Acetic Acid → Carvedilol

Participants

Reaction Steps

To 5 ml dioxane 1.4 g (0.0054 moles) of anhydrous N-2-[2-(methoxy)-phenoxy]-ethyl]-benzylamine, 0.07 g (0.00125 moles) of acetic acid and 0.5 g (0.0021 moles) of 4-(oxiranylmethoxy)-9H-carbazole are added and the reaction mixture is heated to 70-75° C. for 24 hrs (TLC control for checking conversion to N-benzyl carvedilol). To this reaction mixture, a second lot of 0.07 g (0.00125 moles) of acetic acid and 0.5 g (0.0021 moles) of 4-(oxiranylmethoxy)-9H-carbazole are added and the reaction mixture is further heated to 70-75° C. for 24 hrs (TLC control for checking conversion to N-benzyl carvedilol). Dioxane is distilled off from the reaction mixture and to the concentrated reaction mixture 10 ml ethylacetate is added and subjected the reaction mass to hydrogenation. To this solution of N-benzyl carvedilol in ethylacetate, (0.14 g) of wet Pd/C catalyst (5% Pd content and 50% moisture content) is added. The reaction mixture is hydrogenated at 3.5-4.5 Kg/cm2 at temperature of 60-70° C. for a period of about 8 hours. The reaction mixture is filtered and the filtrate is washed with 12-15% v/v aqueous ammonia (1 volume w. r .t. to the carbazole). The product enriched organic layer is separated and concentrated to remove ethylacetate. To the resultant syrupy mass n-butanol (2 ml) is added and the solution is stirred for about 10 hours, the crystals separated by filtration, washed successively with n-butanol (1 ml) and toluene (1 ml) to obtain carvedilol (0.9 g). The product is recrystallized from 3 volumes of ethyl acetate to obtain carvedilol (0.75 g).

Provenance & Evidence